The
goal of FDA's OPD grant program is to support the clinical development of
products for use in rare diseases or conditions where no current therapy
exists or where the product being developed will be superior to the existing
therapy. FDA provides grants for clinical studies on safety and/or
effectiveness that will either result in, or substantially contribute to,
market approval of these products. Applicants must include in the
application's Background and Significance section documentation to support
the assertion that the orphan disease or condition to be studied is a “rare
disease or condition” and an explanation of how the proposed study will
either help support product approval or provide essential data needed for
product development.

Key Dates

Posted Date

August 1, 2012

Open Date (Earliest Submission Date)

December 10, 2012

Letter of Intent Due Date

Not
Applicable.

Application Due Date(s)

Application
Due Date(s): February 6, 2013; February 5, 2014 by
5:00 PM local time of applicant organization.
Resubmission Due Date(s): (Extended to November 8, 2013 per NOT-FD-14-001), Originally
October 15, 2013 and October 15, 2014 by
5:00 PM local time of applicant organization.
This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.

It
is critical that applicants follow the instructions in the SF 424
(R&R) Application Guide, except where instructed to do otherwise.
Conformance to all requirements (both in the Application Guide and the
FOA) is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section IV.
When the program-specific instructions deviate from those in the Application
Guide, follow the program-specific instructions. Applications that do
not comply with these instructions may be delayed or not accepted for review.

NOTICE: Applications
submitted in response to this Funding Opportunity Announcement (FOA) for
Federal assistance must be submitted electronically through Grants.gov
(http://www.grants.gov) using the
SF424 Research and Related (R&R) forms and the SF424 (R&R) Application
Guide.

APPLICATIONS
MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in
conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter
called Grants.gov/Apply).

A
registration process is necessary before submission and applicants are highly
encouraged to start the process at least four (4) weeks prior to the grant
submission date. See Section IV.

The OPD was created to identify and promote the development of orphan products.
Orphan products are drugs, biologics, medical devices, and medical foods that
are indicated for a rare disease or condition. The term “rare disease or
condition” is defined in 21 U.S.C. 360ee. As a practical way to implement the
statutory definition, for devices and foods as well as for drugs, FDA considers
drugs, devices, and medical foods potentially eligible for grants under the OPD
grant program if they are indicated for a disease or condition that has a prevalence,
not incidence, of fewer than 200,000 people in the United States. Diagnostics
and vaccines are considered potentially eligible for such grants only if the U.S. population to whom they will be administered is fewer than 200,000 people in the United States per year.

1.B.
Research Objectives

The goal of FDA's OPD grant program is to support the
clinical development of products for use in rare diseases or conditions where
no current therapy exists or where the proposed product will be superior to the
existing therapy. FDA provides grants for clinical studies on safety and/or
effectiveness that will either result in, or substantially contribute to,
market approval of these products. Applicants must include in the application's
Background and Significance section documentation to support that
the estimated prevalence of the orphan disease or condition in the
United States is less than 200,000 (or in the case of a vaccine or
diagnostic, information to support that the product will be administered to
fewer than 200,000 people in the United States per year),and an explanation
of how the proposed study will either help support product approval or provide
essential data needed for product development. Additional informationmay
be required upon request, for example, regarding population estimate and
rationale. This additional information may be required, in part, to
assure that human clinical trials of drugs are eligible to receive funding
under the OPD grant program. 21 U.S.C. 360ee(b)(1)(A).See Section VIII, Other Information - Required
Federal Citations, for policies related to this announcement.

The OER
Glossary and the SF
424 (R&R) Application Guide provide details on these application
types.

Funds Available and Anticipated Number of Awards

Office
of Orphan Products Development intends to commit $14.1 million in FY 2014
and FY2015.

Of the estimated FY 2014 funding ($14.1 million),
approximately $10 million will fund non-competing continuation awards, and
approximately $4.1 million will fund 5 to 10 new awards, subject to
availability of funds. It is anticipated that funding for the number of
non-competing continuation awards and new awards in FY 2015 will be similar
to FY 2014.

Award Budget

Phase 1 studies are eligible for grants of up to
$200,000 per year for up to 3 years. Phase 2 and 3 studies are eligible for
grants of up to $400,000 per year for up to 4 years. Please note that the
dollar limitation will apply to total costs (direct plus indirect). Budgets
for each year of requested support may not exceed the $200,000 or $400,000
total cost limit, whichever is applicable.

The following definitions are provided to illustrate
drug and biologic products study phases. Devices and medical foods may have
alternative considerations.

Phase 1 studies include the initial introduction of an
investigational new drug (IND) into humans, are usually conducted in healthy
volunteer subjects, and are designed to determine the metabolic and pharmacological
actions of the product in humans, and the side effects, including those
associated with increasing drug doses. In some Phase 1 studies that include
subjects with the rare disorder, it may also be possible to gain early
evidence on effectiveness.

Phase 2 studies include early controlled clinical
studies conducted to: (1) Evaluate the effectiveness of the product for a
particular indication in patients with the disease or condition and (2)
determine the common short-term side effects and risks associated with it.

Phase
3 studies gather more information about effectiveness and safety that is
necessary to evaluate the overall risk-benefit ratio of the product and to
provide an acceptable basis for product labeling.

Award Project Period

The length of support will
depend on the nature of the study. For those studies with an expected
duration of more than 1 year, a second, third, or fourth year of
noncompetitive continuation of support will depend on the following factors:
(1) Performance during the preceding year; (2) compliance with regulatory
requirements of IND/investigational device exemption (IDE), if applicable;
and (3) availability of Federal funds.

In addition to the requirement for an active IND/IDE
discussed in Section V.3 of this document, documentation of assurances with
the Office of Human Research Protection (OHRP) (see Section IV.5.A of this
document) must be on file with the FDA grants management office before an
award is made. Any institution receiving Federal funds must have an institutional
review board (IRB) of record even if that institution is overseeing research
conducted at other performance sites. To avoid funding studies that may not
receive or may experience a delay in receiving IRB approval, documentation of
IRB approval and Federal Wide Assurance (FWA or assurance) for the IRB of
record for all performance sites must be on file with the FDA grants
management office before an award to fund the study will be made. In
addition, if a grant is awarded, grantees will be informed of any additional
documentation that should be submitted to FDA's IRB.

Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the size
and duration of each award will also vary. Although the financial plans of
the FDA provide support for this program, awards pursuant to this funding
opportunity are contingent upon the availability of funds.

The grants are available to any foreign or domestic,
public or private, for-profit or nonprofit entity (including State and local
units of government). Federal agencies that are not part of the Department of
Health and Human Services (HHS) may apply. Agencies that are part of HHS may
not apply. For-profit entities must commit to excluding fees or profit in
their request for support to receive grant awards. Organizations that engage in
lobbying activities, as described in section 501(c)(4) of the Internal Revenue
Code of 1968, are not eligible to receive grant awards.

Applicant
organizations must complete the following registrations as described in the SF
424 (R&R) Application Guide to be eligible to apply for or receive an
award. Applicants must have a valid Dun and Bradstreet Universal Numbering
System (DUNS) number in order to begin each of the following registrations.

All
Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with
their institutional officials to register with the eRA Commons or ensure their
existing eRA Commons account is affiliated with the eRA Commons account of the
applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 4-6 weeks prior to the application due date.

Eligible Individuals
Any individual(s) with the skills, knowledge, and resources necessary to carry
out the proposed research as the PD/PI is invited to work with his/her
organization to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for support.
The Project
Director/Principal Investigator (PD/PI) will be solely
responsible for planning, directing, and executing the proposed project.

Multiple PDs/PIs
The decision of whether to apply for a grant with a single PD/PI or multiple
PDs/PIs grant is the responsibility of the investigators and applicant
organizations and should be determined by the scientific goals of the project.
Applications for grants with multiple PDs/PIs will require additional
information, as outlined in the instructions below. More than one PD/PI (i.e.,
multiple PDs/PIs), may be designated on the application for projects that
require a team science approach and therefore clearly do not fit the
single-PD/PI model. Additional information on the
implementation plans and policies and procedures to formally allow more than
one PD/PI on individual research projects is available at https://grants.nih.gov/grants/multi_pi.

When multiple PDs/PIs are proposed, FDA requires one
PD/PI to be designated as the "Contact PI, who will be responsible for all
communication between the PDs/PIs and the FDA, for assembling the application
materials outlined below, and for coordinating progress reports for the
project. The contact PD/PI must meet all eligibility requirements for PD/PI
status in the same way as other PDs/PIs, but has no other special roles or
responsibilities within the project team beyond those mentioned above.

Information for the
Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons
prior to application submission. The Commons ID of each PD/PI must be included in the
Credential field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application
to be rejected.
All projects proposing Multiple PDs/PIs
will be required to include a new section describing the leadership plan approach for
the proposed project.

Multiple PD/PI
Leadership Plan
For applications designating multiple PDs/PIs, a new section of the research
plan, entitled Multiple PD/PI Leadership Plan [Section 14 of the Research Plan
Component in the SF424 (R&R)], must be included. A rationale for choosing a
multiple PD/PI approach should be described. The governance and
organizational structure of the leadership team and the research project should
be described, and should include communication plans, process for making
decisions on scientific direction, and procedures for resolving
conflicts. The roles and administrative, technical, and scientific
responsibilities for the project or program should be delineated for the
PDs/PIs and other collaborators.

If budget allocation
is planned, the distribution of resources to specific components of the project
or the individual PDs/PIs should be delineated in the Leadership Plan. In the
event of an award, the requested allocations may be reflected in a footnote on
the Notice of Award (NoA).

Applications Involving a Single InstitutionWhen
all PDs/PIs are within a single institution, follow the instructions contained
in the SF424 (R&R) Application Guide.

Applications Involving Multiple InstitutionsWhen multiple institutions are
involved, one institution must be designated as the prime institution and
funding for the other institution(s) must be requested via a subcontract to be
administered by the prime institution. When submitting a detailed budget, the
prime institution should submit its budget using the Research & Related
Budget component. All other institutions should have their individual
budgets attached separately to the Research & Related Subaward Budget
Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application
Guide for further instruction regarding the use of the subaward budget
form.

Number of Applications
Applicant
organizations may submit more than one application, provided each application
is scientifically distinct.

FDA
will not accept any application in response to this FOA that is essentially the
same as one currently pending initial peer review unless the applicant
withdraws the pending application. FDA will not accept any application that is
essentially the same as one already reviewed.

Section IV.
Application and Submission Information

To
comply with the President’s Management Agenda, HHS is participating as a
partner in the new government-wide grants.gov application site. Applicants
should apply electronically by visiting the web site www.grants.gov and following instructions under Apply for Grants. Users of grants.gov
will be able to download a copy of the application package, complete it offline,
and then upload and submit the application via the grants.gov web site. We
strongly encourage using the Tips posted on www.grants.gov under the
announcement number when preparing your submission. This process is similar to
the R01 Grant Application process currently used at the National Institutes of
Health (NIH). You can visit the following website for helpful background
on preparing to apply, preparing an application, and submitting an application
to Grants.gov: http://era.nih.gov/ElectronicReceipt/.
In order to apply electronically, the applicant must have a Data Universal
Number System (DUNS) number, and register in the Central Contractor
Registration (CCR) database, in eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm),
and in grants.gov (further information below).

A registration process with Grants.gov and eRA Commons is necessary before submission and applicants are highly encouraged to start
the process at least four weeks prior to the grant submission
date. PDs/PIs should work with their institutions/organizations
to make sure they are registered in the eRA Commons.

Several additional separate actions are required before
an applicant institution/organization can submit an electronic application, as
follows:

The individual(s) designated as PDs/PIs on the
application must also be registered in the eRA Commons. In the case of
multiple PDs/PIs, all PDs/PIs must be registered in the eRA Commons prior to
the submission of the application.

Each PD/PI must hold a PD/PI account in the Commons.
Applicants should not share a Commons account for both an Authorized
Organization Representative/Signing Official (AOR/SO) role and a PD/PI role;
however, if they have both a PD/PI role and an Internet Assisted Review (IAR)
role, both roles should exist under one Commons account. When multiple PDs/PIs
are proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must be done by the AOR/SO
or their designee who is already registered in the Commons.

Both the PD/PI(s) and AOR/SO need separate accounts in
the eRA Commons since both are authorized to view the application image.
Note that if a PD/PI is already registered in the eRA Commons, another
registration to apply for an FDA opportunity is not necessary.

Several of the steps of the registration process could
take four weeks or more. Therefore, applicants should immediately check with
their business official to determine whether their organization/institution is
already registered in both Grants.gov and the Commons (https://commons.era.nih.gov/commons/).
The FDA will accept electronic applications only from organizations that have
completed all necessary registrations.

If you experience technical difficulties with your
online submission, you should contact the grants.gov Customer Response Center http://www.grants.gov/web/grants/support.html. If the Customer Response Center is unable to resolve your problem, please contact Vieda Hubbard,
Grants Management Specialist, Division of Acquisition Support and Grants
(DASG), Office of Acquisition and Grant Services (OAGS), Food and Drug
Administration, at 301-827-7177, or by e-mail at vieda.hubbard@fda.hhs.gov.

1. Requesting an
Application Package

Applicants
must download the SF424 (R&R) application package associated with this
funding opportunity using the “Apply for Grant Electronically” button in this
FOA or following the directions provided at Grants.gov.

In FY 2014 and 2015, all applications must be submitted
electronically through Grants.gov. Applicants must download the SF424 (R&R)
application forms and the SF424 (R&R) Application Guide for this FOA
through http://www.grants.gov/web/grants/applicants/apply-for-grants.html.

Note: Only the forms package directly attached to a
specific FOA can be used. You will not be able to use any other SF424 (R&R)
forms (e.g., sample forms, forms from another FOA). Please locate the
current package each cycle to obtain the most up to date forms to download and
submit. Forms may change between receipt dates.

For further assistance, contact: Vieda Hubbard at 301-827-7177.
Telecommunications for the hearing impaired: 301-480-0434.

2. Content and Form of Application
Submission

It
is critical that applicants follow the instructions in the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

The SF424 (R&R) Application Guide is critical to
submitting a complete and accurate application to FDA. Some fields within the
SF424 (R&R) application components, although not marked as mandatory, are
required by FDA (e.g., the Credential log-in field of the Research &
Related Senior/Key Person Profile component must contain the PD/PIs assigned
eRA Commons User ID). Agency-specific instructions for such fields are clearly
identified in the Application Guide. For additional information, see Frequently
Asked Questions“ Application Guide, Electronic Submission of Grant Applications (https://grants.nih.gov/grants/ElectronicReceipt/faq_full.htm#application).

Special instructions for applicants who are submitting a
renewal or revisionApplicants submitting a renewal or resubmission are
required to enter the previous grant number into the Federal Identifier field
in the SF424 (R&R) Cover Component form (box #8). Renewal and
resubmission applications that do not include this number will receive an error
message. Applicants should log on to the eRA Commons to obtain the
previous grant number. If the number is not available in Commons, contact Vieda
Hubbard, 301- 827-7177 at FDA to get the previous grant number in order to
submit the application. Visit http://era.nih.gov/ElectronicReceipt/resubmission_FAQ.htm for additional information. If an application for the same study was
submitted in response to a previous request for application (RFA) but has not
yet been funded, an application in response to this notice will be considered a
request to withdraw the previous application. The applicant for a resubmitted
application should address the issues presented in the summary statement from
the previous review and include a copy of the summary statement itself as part
of the resubmitted application. A resubmission application should be
complete and stand alone from previous versions. An application that has
received two prior disapprovals is not eligible for resubmission.

Prepare all applications using the SF424 (R&R)
application forms and in accordance with the SF424 (R&R) Application Guide
for this FOA through http://www.grants.gov/web/grants/applicants/apply-for-grants.html. Please
locate the current package each cycle to obtain the most up-to-date forms to
download and submit. Forms may change between receipt dates.

Note that the move to electronic applications has brought
a change in terminology. The Grants.gov terminology is as follows:

The
forms package associated with this FOA includes all applicable components,
mandatory and optional. The SF424 (R&R) application has several components.
Some components are required, others are optional. The forms package associated
with this FOA in http://www.grants.gov/web/grants/applicants/apply-for-grants.htmlincludes
all applicable components, required and optional. Follow all instructions in
the SF424 (R&R) Application Guide to ensure you complete all appropriate
“optional” components. A completed application in response to this FOA includes
the data in the following components:

Prepare detailed budgets for all applications (that is,
complete the Research & Related Budget component of the SF424).

Not seek charge back of customs and import fees.

Make every effort to comply with the format
specifications, which are based upon a standard U.S. paper size of 8.5 x 11
within each PDF.

Comply with Federal/FDA policies on human subjects,
animals, and biohazards.

Comply with Federal/FDA biosafety and biosecurity
regulations. See Section VI.2., Administrative and National Policy
Requirements.

Indicate in the 398 Research Plan how the proposed
project has specific relevance to the mission and objectives of FDA and has the
potential for significantly advancing sciences in the United States.

Proposed research should provide special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions in other countries that are not
readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs
See Section III.1.B

Page Limitations

All
page limitations described in the SF424 Application Guide and the Table of
Page Limits must be followed, with the following exceptions or additional
requirements:

For this specific FOA, the Research Strategy section is limited
to 25 pages.

PHS 398 Research Plan Component All instructions in the SF424
(R&R) Application Guide must be followed, with the following additional
instructions:

Page limitations of
the PHS398 Research Plan component must be followed as outlined in the SF424
(R&R) Application Guide unless otherwise stated per FDA’s guidelines
located at http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/WhomtoContactaboutOrphanProductDevelopment/ucm186346.htm.
Although each section of the Research Plan component needs to be uploaded
separately as a PDF attachment, applicants are encouraged to construct the
Research Plan component as a single document, separating sections into distinct
PDF attachments just before uploading the files. This approach will enable
applicants to better monitor formatting requirements such as page limits. All
attachments must be provided to FDA in PDF format, filenames must be included
with no spaces or special characters, and a .pdf extension must be
used.

Do not use the Appendix to circumvent the page
limitations of the Research Plan component. An application
that does not observe the required page limitations may be delayed in the
review process.

Foreign Institutions

Indicate how the
proposed project has specific relevance to the mission and objectives of FDA
and has the potential for significantly advancing sciences in the United
States.

3. Submission Dates and Times

Part I. Overview Information contains information
about Key Dates. Applicants are encouraged to submit in advance of the deadline
to ensure they have time to make any application corrections that might be
necessary for successful submission.

Organizations
must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure
accurate and successful submission.

Information
on the submission process and a definition of on-time submission are provided
in the SF424 (R&R) Application Guide.

3.A. Submission, Review, and
Anticipated Start Dates
Opening Date: December
6, 2013 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable.
Application Due Date(s): February 6, 2013 and February 5,
2014
Resubmission
Due Date(s): October 15, 2013 and October 15, 2014
Peer Review Date(s): May 2013 and 2014 and November 2013 and
2014
Council Review Date(s): September 2013 and 2014 and
February 2014 and 2015
Earliest Anticipated Start Date(s): November
2013 and November 2014

Please note that there is only one receipt date for FY 2014
and one receipt date for FY 2015 for new and resubmitted applications. Resubmissions
and applications that were submitted previously will be allowed to resubmit
October 15, 2013 and October 15, 2014. Resubmissions will also be accepted in
the February receipt dates in both Fiscal years.

NOTE: On time submission requires that applications be
successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the
applicant institution/organization). Applications
must be received by the close of business on the established receipt
date. Late applications may be accepted under extreme circumstances
beyond the control of the applicant. Applications not received on time
will not be considered for review and will generally be returned to the
applicant.

The protocol in the grant application should be submitted
to the IND/IDE no later than January 7, 2013 for FY 2014 and no later than
January 6, 2014 for FY 2015. The
current version of the protocol that is included in the grant application and
is intended to be used if the study is funded is the protocol that MUST be
submitted to the IND/IDE before the application is reviewed. The date that corresponds with the
IND/IDE submission/amendment date that corresponds to the protocol in the grant
application should be reported in the title of the grant with the IND/IDE
number. For resubmissions, if any changes to the protocol have occurred since
the last review, the protocol must be resubmitted as an amendment to the
IND/IDE prior to the October resubmission dates.

In order to expedite the review, applicants are requested
to notify the FDA
Referral Office by email vieda.hubbard@fda.hhs.gov when the application has been submitted. Please include the FOA
number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00
p.m. local time (of the applicant
institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due
date(s) and time, the application may be delayed in the review process or not
reviewed.

Once an application package has been successfully
submitted through Grants.gov, any errors have been addressed, and the assembled
application has been created in the eRA Commons, the PD/PI and the Authorized
Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday-
Friday, excluding Federal holidays) to view the application image to determine
if any further action is necessary.

If everything is acceptable, no further action is
necessary. The application will automatically move forward for processing after
two business days, excluding Federal holidays.

Prior to the submission deadline, the AOR/SO can Reject
the assembled application and submit a changed/corrected application within the
two day viewing window. This option should be used if it is determined that
some part of the application was lost or did not transfer correctly during the
submission process, the AOR/SO will have the option to Reject the application
and submit a Changed/Corrected application. In these
cases, please contact the eRA Help Desk to ensure that the issues are addressed
and corrected. Once rejected, applicants should follow the instructions for
correcting errors in Section 2.12 of the SF424 (R&R) Application Guide (https://grants.nih.gov/grants/funding/424/index.htm#),
including the requirement for cover letters on late applications. The
Reject feature should also be used if you determine that warnings are
applicable to your application and need to be addressed now. Remember,
warnings do not stop further application processing. If an application
submission results in warnings (but no errors), it will automatically move
forward after two weekdays if no action is taken. Some warnings may need to be
addressed later in the process. If the two day window falls after the
submission deadline, the AOR/SO will have the option to Reject the application
if, due to an eRA Commons or Grants.gov system issue, the application does not
correctly reflect the submitted application package (e.g., some part of the
application was lost or didn’t transfer correctly during the submission
process). The AOR/SO should first contact the eRA Commons Helpdesk (http://ithelpdesk.nih.gov/eRA/)
to confirm the system error, document the issue, and determine the best course
of action. FDA will not penalize the applicant for an eRA Commons or Grants.gov
system issue.

If the AOR/SO chooses to Reject the image after the
submission deadline for a reason other than an eRA Commons or Grants.gov system
failure, a changed/corrected application still can be submitted but it will be
subject to the NIH/FDA late policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-030.html)
guidelines and may not be accepted. The reason for this delay should be
explained in the cover letter attachment. Late
applications may be accepted under extreme circumstances beyond the control of
the applicant. In the absence of such extreme circumstances beyond the
applicant's control, applications not received on time will not be considered
for review and will generally be returned to the applicant.

Both the AOR/SO and PD/PI will receive e-mail
notifications when the application is rejected or the application automatically
moves forward in the process after two days.

In unusual circumstances, additional information may be
considered, on a case by case basis, for inclusion in the ad hoc expert panel
review, however, the FDA cannot assure inclusion of any information after the
receipt date other than evidence of final IRB approval, FWA or assurance, and
certification of adequate supply of study product.

Upon receipt, applications will be evaluated for
completeness. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov
and the Commons. The submitting AOR receives
the Grants.gov acknowledgments. The AOR and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the
responsibility of the applicant to check periodically on their application
status in the Commons.

FDA will not accept any application in response to this
FOA that is essentially the same as one currently pending initial merit review
unless the applicant withdraws the pending application. FDA will not accept any
application that is essentially the same as one already reviewed. However,
the FDA will accept a resubmission application, but such application must
include an Introduction (1 page maximum) addressing
the critique from the previous review.

All FDA awards are subject to the terms
and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement.

5.A. Protection of Human Research
Subjects

All
institutions engaged in human subject research financially supported by HHS
must file an assurance of protection for human subjects with the Office of
Human Research Protections (OHRP) (45 CFR part 46). Applicants are advised to
visit the OHRP Web site at http://www.hhs.gov/ohrp for
guidance on human subject protection issues. Federal regulations (45 CFR 46)
require that applications and proposals involving human subjects must be
evaluated with reference to the risks to the subjects, the adequacy of
protection against these risks, the potential benefits of the research to the
subjects and others, and the importance of the knowledge gained or to be gained
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html ).

The requirement to file an assurance
applies to both awardee and collaborating performance site institutions.
Awardee institutions are automatically considered to be engaged in human
subject research whenever they receive a direct HHS award to support such
research, even where all activities involving human subjects are carried out by
a subcontractor or collaborator. In such cases, the awardee institution bears
the responsibility for protecting human subjects under the award.

The awardee institution is also
responsible for, among other things, ensuring that all collaborating
performance site institutions engaged in the research hold an approved
assurance prior to their initiation of the research. No awardee or performance
site institution may spend funds on human subject research or enroll subjects
without the approved and applicable assurance(s) on file with OHRP. An awardee
institution must, therefore, have its own IRB of record and assurance. The IRB
of record may be an IRB already being used by one of the performance sites, but
it must specifically be registered as the IRB of record with OHRP.

For further information, applicants
should review the section on human subjects in the application instructions as
posted on the Grants.gov application Web site. The clinical protocol should
comply with ICHE6 Good Clinical Practice Consolidated Guidance which sets an
international ethical and scientific quality standard for designing,
conducting, recording, and reporting trials that involve the participation of
human subjects. All human subject research regulated by FDA is also subject to
FDA's regulations regarding the protection of human subjects (21 CFR parts 50
and 56). Applicants are encouraged to review the regulations, guidance, and
information sheets on human subject protection and good clinical practice
available on the Internet at http://www.fda.gov/oc/gcp/.

5.B.
Key Personnel and Human Subject Protection Education

The awardee institution is responsible for ensuring that all key personnel
receive appropriate training in their human subject protection responsibilities.
Key personnel include all principal investigators, co-investigators, and
performance site investigators responsible for the design and conduct of the
study. HHS, FDA, and OPD do not prescribe or endorse any specific education
programs. Many institutions have already developed educational programs on the
protection of research subjects and have made participation in such programs a
requirement for their investigators. Other sources of appropriate instruction
might include the online tutorials offered by the Office of Human Subjects
Research, NIH at http://ohsr.od.nih.gov/ and by OHRP at http://www.hhs.gov/ohrp/education/.

Within 30 days of the award, the
principal investigator should provide a letter to FDA's grants management
office that includes the names of the key personnel, the title of the human
subjects protection education program completed for each key personnel, and a
one-sentence description of the program. This letter should be signed by the
principal investigator and cosigned by an institution official and sent to the
Grants Management Specialist whose name appears on the official Notice of Grant
Award (NGA).

6. Other Submission Requirements and
Information

Applications
must be submitted electronically following the instructions described in the SF
424 (R&R) Application Guide. Paper
applications will not be accepted.

For
assistance with your electronic application or for more information on
the electronic submission process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the SF
424(R&R) Application Package.Failure to register in the Commons and
to include a valid PD/PI Commons ID in the credential field will prevent the
successful submission of an electronic application to FDA.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications
will be evaluated for completeness. Applications that are incomplete will
not be reviewed.

6.A. Informed Consent

Consent forms, assent forms, and any other information given to a subject are
part of the grant application and must be provided, even if in a
draft form. The consent forms should be attached in an appendix section. The
applicant is referred to HHS and FDA regulations at 45 CFR 46.116 and 21 CFR
50.25 for details regarding the required elements of informed consent.

6.C. Organizational DUNS
The applicant organization must include its DUNS number in
its Organization Profile in the eRA Commons. This DUNS number must match the
DUNS number provided at CCR registration with Grants.gov. For additional
information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant
Applications.

Section V.
Application Review Information

1. General InformationFDA
grants management and program staff will review all applications sent in
response to this notice. To be responsive, an application must be submitted in
accordance with the requirements of this notice. Applications found to be
non-responsive will receive notice that the application will not be reviewed.

Applicants are strongly encouraged to contact FDA to
resolve any questions about criteria before submitting their application.
Please direct all questions of a technical or scientific nature to the OPD
program staff and all questions of an administrative or financial nature to the
grants management staff (see Agency Contacts in Section VII of this document).

Responsive
applications will be reviewed and evaluated for scientific and technical merit
by an ad hoc panel of experts in the subject field of the specific application.
Consultation with the proper FDA review division may also occur during this
phase of the review to determine whether the proposed study will provide
acceptable data that could contribute to product approval. Responsive
applications may be subject to a second review by the National Cancer
Institute, National Cancer Advisory Board (NCAB) for concurrence with the
recommendations made by the first-level reviewers, and funding decisions will
be made by the Commissioner of Food and Drugs or his designee. By submitting an application in response to this RFA,applicants
understand and agree that members of the ad hoc panel of experts and the NCAB may
be provided access to non-public information contained in the grant
application, as necessary for evaluation of the application and subject to
necessary restrictions on the further disclosure of the information.

A score will be assigned to each application based on the
scientific/technical review criteria. The review panel may advise the program
staff about the appropriateness of the proposal to the goals of the OPD grant
program.

Applications submitted
in response to this FOA will compete for available funds with all other
recommended applications submitted in response to this FOA. The following will
be considered in making funding decisions:

Scientific merit of the proposed project as determined by
peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

The goal of FDA's OPD grant program is to support the clinical
development of products for use in rare diseases or conditions where no current
therapy exists or where the product will be superior to the existing therapy.
In
their written critiques, reviewers will be asked to comment on each of the
following criteria in addition to the Scientific/Technical Review Criteria
outlined below, in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. Each of these
criteria will be addressed and considered in assigning the overall score, and
weighted as appropriate for each application. Note that an application does not
need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a meritorious priority score.

Investigators: Assessing the competence of the principal investigator(s)
and key personnel to conduct the proposed research. This includes their
academic qualifications, research experiences, productivity, and any special
attributes.

Resources and Environment: Evaluating any special attributes or deficiencies
relevant to the conduct of the proposed studies.

Budget: Evaluating
whether all items of the requested budget are appropriate and justified.

Human Subjects
and Monitoring: Evaluating
possible physical, psychological, or social injury patients might experience as
subjects in the proposed research. Discussing whether the rights and
welfare of the individuals will be adequately protected. Assessing the
safety-monitoring plan including the reporting of adverse events. Evaluating
the informed consent documents as well as the plan to monitor the integrity of
the data collected and the compliance with the protocol.

2. Scientific/Technical Review Criteria

The ad
hoc expert panel will review the application based on the following scientific
and technical merit criteria:

1. The soundness of the rationale for the proposed study;

2. The quality and appropriateness of the study design,
including the design of the monitoring plans;

3. The statistical justification for the number of
patients chosen for the study, based on the proposed outcome measures, and the
appropriateness of the statistical procedures for analysis of the results;

4. The adequacy of the evidence that the proposed number
of eligible subjects can be recruited in the requested timeframe;

5. The qualifications of the investigator and support
staff, and the resources available to them;

6. The adequacy of the justification for the request for
financial support;

7. The adequacy of plans for complying with regulations
for protection of human subjects and monitoring; and

8. The ability of the applicant to complete the proposed
study within its budget and within time limits stated in this FOA.

2. There must be an explanation in the Background and
Significance section of how the proposed study will either contribute to
product approval or provide essential data needed for product development.

3. The Background and Significance section of the
application must contain information documenting that the disease or condition
to be treated meets the definition of a rare disease or condition, as defined
in 21 U.S.C. 360ee. FDA generally considers drugs, devices, and medical foods
potentially eligible for grants under the OPD grant program if they are
indicated for a disease or condition that has a prevalence, not incidence, of
fewer than 200,000 people in the United States. Diagnostics and vaccines are
considered potentially eligible for such grants only if the U.S. population to whom they will be administered is fewer than 200,000 people in the United States per year.

4. With the exception noted below, the study protocol
proposed in the grant application must be under an active IND or IDE (not on
clinical hold) to qualify the application for scientific and technical review.
Additional IND/IDE information is described as follows:

The proposed clinical protocol should be submitted to the
applicable FDA IND/IDE review division a minimum of 30 days before the grant
application deadline. The number assigned to the IND/IDE that includes
the proposed study should appear on the face page of the application with the
title of the project. The date the subject protocol was submitted to FDA
for the IND/IDE review should also be provided. Protocols that would
otherwise be eligible for an exemption from the IND regulations must be
conducted under an active IND to be eligible for funding under this FDA grant
program. If the sponsor of the IND/IDE is other than the principal
investigator listed on the application, a letter from the sponsor permitting
access to the IND/IDE must be submitted in both the IND/IDE and in the grant
application. The name(s) of the principal investigator(s) named in the
application and in the study protocol must be submitted to the IND/ IDE. Studies of already approved products, evaluating new orphan indications,
are also subject to these IND/IDE requirements.

Only medical foods that do not need pre-market approval
and medical devices that are classified as non-significant risk (NSR) are free
from these IND/IDE requirements. Applicants studying an NSR device should
provide a letter in the application from the FDA Center for Devices and
Radiologic Health indicating the device is an NSR device.

5. The requested budget must be within the limits, either
$200,000 in total costs per year for up to 3 years for any phase study, or
$400,000 in total costs per year for up to 4 years for Phase 2 or 3 studies.
Any application received that requests support over the maximum amount
allowable for that particular study will be considered non-responsive.

6. In an appendix to the application, there must be
evidence that the product to be studied is available to the applicant in the
form and quantity needed for the clinical trial proposed. A current
letter from the supplier as an appendix will be acceptable. If negotiations
regarding the supply of the study product are underway but have not been
finalized at the time of application, please provide a letter indicating such
in the application. Verification of adequate supply of study product will be
necessary before an award is made.

8. Additional information may be required
upon request, for example, regarding population estimate and rationale. This additional information may be
required, in part, to assure that human clinical trials of drugs are eligible
to receive funding under the OPD grant program. 21 U.S.C. 360ee(b)(1)(A).

4. Additional Review Criteria
As
applicable for the project proposed, reviewers will evaluate the following
additional items while determining scientific and technical merit, and in
providing an overall impact/priority score, but will not give separate scores
for these items.

Protection of Human SubjectsFor research that involves human subjects but does not
involve one of the six categories of research that are exempt under 45 CFR Part
46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the
criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials. For additional information on review of the Human Subjects section,
please refer to the Human Subjects Protection and Inclusion Guidelines. See the
Human Subjects Sections of the PHS398 Research Plan component of the SF424
(R&R).

Inclusion of Women, Minorities and Children in Research
The committee will evaluate the proposed plans
for inclusion of minorities
and members of both genders, as well as the inclusion of children as
appropriate for the scientific goals of the research will be assessed. Plans
for the recruitment and retention of subjects will also be evaluated. See the
Human Subjects Sections of the PHS398 Research Plan component of the SF424
(R &R). For
additional information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Biohazards
Reviewers will assess whether materials or procedures proposed are potentially
hazardous to research personnel and/or the environment, and if needed,
determine whether adequate protection is proposed.

Resubmissions
For Resubmissions, the committee will evaluate the application as now
presented, taking into consideration the responses to comments from the
previous scientific review group and changes made to the project. The adequacy
of the responses to comments from the most recent scientific review group will
be assessed including the appropriateness of the improvements in the
resubmission application.

Applicants may submit a resubmission application, but
such application must include an Introduction addressing the previous peer
review critique (Summary Statement). The Summary Statement must be
included as an Appendix in the application.

Resubmissions
are intended for those applications that were previously submitted to OPD,
reviewed and received a score on the application.

Renewals

Renewal
applications will be permitted for this FOA. For Renewals, the committee will consider the progress
made in the last funding period.

Revisions

For Revisions, the committee
will consider the appropriateness of the proposed expansion of the scope of the
project. If the Revision application relates to a specific line of investigation
presented in the original application that was not recommended for approval by
the committee, then the committee will consider whether the responses to
comments from the previous scientific review group are adequate and whether
substantial changes are clearly evident.

Active
grants in regulatory compliance may be eligible to submit a competing
supplement application. A competing supplement (also called Revision) is a
request for additional funds for a current award to expand the scope of work.
Competing supplements may be submitted throughout the fiscal year and will be
permitted for this FOA to compete for funding. Please contact the OPD program
contact for further information.

5.
Additional Review Considerations
As
applicable for the project proposed, reviewers will consider each of the
following items, but will not give scores for these items, and should not
consider them in providing an overall impact/priority score.

Applications from Foreign Organizations
Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions in other
countries that are not readily available in the United States or that augment
existing U.S. resources.

Resource Sharing Plans

Not
applicable

Budget and Period of Support
Reviewers
will consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research. The
priority score should not be affected by the evaluation of the budget.

6. Review
and Selection Process

Applications will be evaluated for scientific and technical merit by
appropriate Scientific Review Groups, using the stated review
criteria.

Applications will compete for available funds with all other
recommended applications submitted in response to this FOA. Following initial
peer review, recommended applications will receive a second level of review by
the appropriate national Advisory Council or Board. The following will be
considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

7. Anticipated Announcement and Award
Dates

After
the peer review of the application is completed, the PD/PI will be able to
access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, FDA
may request information from the applicant prior to making the award. For
details, applicants may refer to the HHS Grants
Policy Statement.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Awardees
must comply with any funding restrictions described in Section
IV.5. Funding Restrictions. Selection of
an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award
costs. See Section IV.5., Funding Restrictions.

After
the review of the application is completed, the PD/PI will be able to access
his or her Summary Statement (written critique) via the eRA Commons.

2. Administrative and National Policy Requirements

All FDA grant and cooperative agreement awards include
the HHS Grants Policy Statement as part of the NoA. For these terms of
award, see the HHS Grants
Policy Statement.

A
final progress report, invention statement, and the expenditure data portion of
the Federal Financial Report are required for closeout of an award, as
described in the HHS Grants
Policy Statement.

The
Federal Funding Accountability and Transparency Act of 2006 (Transparency Act),
includes a requirement for awardees of Federal grants to report information
about first-tier subawards and executive compensation under Federal assistance
awards issued in FY2011 or later. All awardees of applicable FDA grants and
cooperative agreements are required to report to the Federal Subaward
Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.

3.A. Monitoring Activities

The guidelines
below are intended to provide information for principal investigators who are
conducting clinical trials. The procedures outlined herein are in addition to
(and not in lieu of) Institutional Review Board (IRB), Office for Human
Research Protections (OHRP), other Food and Drug Administration (FDA), and Good
Clinical Practices requirements.

It is an OPD policy that data and safety monitoring of a
clinical trial is to be commensurate with the risks posed to study participants
and with the size and complexity of the study. In addition, the OPD requires
that a Grantee and any third party engaged in supporting the clinical research
be responsible for oversight of data and safety monitoring, ensuring that
monitoring systems are in place, that the quality of the monitoring activity is
appropriate, and that the OPD Project Officer is informed of recommendations
emanating from monitoring activities.

3.A.1. FDA Requirements for Monitoring

The OPD
requires that each clinical trial it supports, regardless of phase, has data
and safety monitoring procedures in place to safeguard the well-being of study
participants and to ensure scientific integrity. Monitoring must be performed
on a regular basis throughout the subject accrual, treatment, and follow-up
periods.

The specific approach
to monitoring will depend on features of the clinical trial to be conducted
e.g., several levels of monitoring: Data and Safety Monitoring Board (DSMB),
Study Monitoring Committee (SMC) and Independent Medical Monitor (IMM). Monitoring
activities should be appropriate to the study, study phase, population,
research environment, and degree of risk involved. Guidance is available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf.

In small, single-site studies, safety monitoring is often
performed by the independent medical monitor or a safety monitoring committee
in conjunction with the study statistician. Phase 3 studies and high risk Phase
1 or 2 clinical trials frequently use a DSMB. It may be desirable to utilize a
DSMB for:

The
OPD requires that the protocol document include a section describing the
proposed plan for interim data monitoring. This section will detail who is to
be responsible for interim monitoring (i.e., a DSMB, an SMC, or the study
investigator), what data will be monitored (i.e., performance and safety data
only vs. efficacy data as well), the timing of the first data review (e.g.,
"the first interim look will occur when the initial 20 participants have
completed the 6 month follow-up visit"), and the frequency of interim
reviews (which will depend on such factors as the study design, interventions
and anticipated recruitment rate). The plan will specify "stopping
guidelines" and other criteria for the monitors to follow in their review
of the interim data. Guidance on these topics is available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127073.pdf.

A preliminary monitoring plan must be
submitted as part of the Research Plan portion of the grant application for a
clinical trial. The plan will be examined as part of the peer review process,
and any comments and concerns will be included in an administrative note in the
summary statement. OPD staff will ensure that all concerns
are resolved before the grant award is made.

3.B. Oversight Activities

The
program project officer will monitor grantees periodically. The monitoring may
be in the form of telephone conversations, e-mails, or written correspondence
between the project officer/grants management officer or specialist and the
principal investigator. Information including, but not limited to, information
regarding study progress, enrollment, problems, adverse events, changes in
protocol, and study monitoring activities will be requested. Periodic site
visits with officials of the grantee organization may also occur. The results
of these monitoring activities will be recorded in the official grant file and
will be available to the grantee upon request consistent with applicable
disclosure statutes and with FDA disclosure regulations. Also, the grantee
organization must comply with all special terms and conditions of the grant,
including those which state that future funding of the study will depend on recommendations
from the OPD project officer. The scope of the recommendations will consider the
following: (1) progress toward enrollment, based on specific circumstances of
the study; (2) adequate supply of the product/device; and (3) compliance with
applicable FDA and HHS regulatory requirements for the trial.

In addition to the requirement for an active IND/IDE
discussed in Section V.3 of this document, documentation of assurances with the
Office of Human Research Protection (OHRP) (see Section IV.5.A of this
document) must be on file with the FDA grants management office before an award
is made. Any institution receiving Federal funds must have an institutional
review board (IRB) of record even if that institution is overseeing research
conducted at other performance sites. To avoid funding studies that may not
receive or may experience a delay in receiving IRB approval, documentation of
IRB approval and Federal Wide Assurance (FWA or assurance) for the IRB of
record for all performance sites must be on file with the FDA grants management
office before an award to fund the study will be made. In addition, if a grant
is awarded, grantees will be informed of any additional documentation that
should be submitted to FDA's IRB.

3.C. Reporting Requirement

The grantee
must file a final program progress report, financial status report, and
invention statement within 90 days after the end date of the project period as
noted on the notice of grant award.

When multiple years are involved, awardees will be
required to submit the Non-Competing Grant Progress Report (PHS 2590) annually
and financial statements as required in the HHS Grants Policy Statement, dated January
1, 2007 (http://www.hhs.gov/grantsnet/adminis/gpd/).
Also, all new and continuing grants must comply with all regulatory
requirements necessary to keep the status of their IND/IDE active and in
effect, that is, not on clinical hold. Failure to meet regulatory requirements
will be grounds for suspension or termination of the grant.

The Food and Drug Administration Amendments Act of 2007 (FDAAA) contains
provisions that expand the current database known as ClinicalTrials.gov to
include additional requirements for individuals and entities, including
grantees, who are involved in conducting clinical trials that involve products
regulated by FDA or that are funded by the Department of Health and Human
Services (HHS), including FDA. These additional requirements include
mandatory registration of certain types of clinical trials, as well as
reporting of results for certain trials for inclusion in the ClinicalTrials.gov
database. ClinicalTrials.gov, which was created after the Food and Drug
Administration Modernization Act of 1997, provides patients, family members,
healthcare providers, researchers, and members of the public easy access to
information on clinical trials for a wide range of diseases and conditions. The
U.S. National Library of Medicine (NLM) has developed this site in
collaboration with NIH and FDA. ClinicalTrials.gov is available to the public
through the Internet at http://clinicaltrials.gov.

ClinicalTrials.gov contains information about certain
clinical trials, both federally and privately funded, of drugs (including
biological products) and medical devices. The types of trials that are
required to be registered, and for which results must be reported, are known as
"applicable clinical trials." FDAAA defines the types of
clinical trials that are "applicable clinical trials" and, therefore,
are subject to the registration and results reporting requirements. The
registry listing for each trial includes information such as descriptive
information about the trial, patient eligibility criteria, recruitment status,
location information on the clinical trial sites, and points of contact for
those wanting to enroll in the trial. The database also contains
information on the results of clinical trials. More detailed information
on the definition of "applicable clinical trial" and the registry and
results reporting requirements can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html and http://prsinfo.clinicaltrials.gov/fdaaa.html.

FDAAA also added new requirements concerning clinical
trials supported by grants from HHS, including FDA. Under these
provisions, any grant or progress report forms required under a grant from any
part of HHS, including FDA, must include a certification that the person
responsible for entering information into ClinicalTrials.gov (the "responsible
party") has submitted all required information to the database.
There are also provisions regarding when agencies within HHS, including FDA,
are required to verify compliance with the database requirements before
releasing funding to grantees. OPD program staff will be providing
additional information on these requirements, including the appropriate means
by which to certify that a grantee has complied with the database requirements.

1.B. Data and Safety Monitoring
Plan

See
Section VI.3.A. for more detail and other FDA monitoring requirements.
The establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risk
to the participants, and generally for Phase 3 clinical trials. Although Phase 1
and Phase 2 clinical trials may also use DSMBs, smaller clinical trials may not
require this oversight format, and alternative monitoring plans may be
appropriate.

1.C. Access to Research Data
through the Freedom of Information Act (FOIA)

The Freedom of Information Act (FOIA), 5 U.S.C. 552, provides individuals with
a right to access certain records in the possession of the Federal government,
subject to certain exemptions. The government may withhold information pursuant
to the exemptions and exclusions contained in the FOIA. The exact language of
the exemptions can be found in the FOIA. Additional guidance on the exemptions
and how they apply to certain documents can be found in the HHS regulations
implementing the FOIA (45 CFR part 5) and FDA regulations implementing the
FOIA (21 CFR part 20). (Also see the HHS Web site http://www.hhs.gov/foia/ and FDA Web site at http://www.fda.gov/RegulatoryInformation/FOI/default.htm )

Data included in the application may be considered trade
secret or confidential commercial information within the meaning of relevant
statutes and implementing regulations. FDA will protect trade secret or
confidential commercial information to the extent allowed under applicable law.

Applicants for PHS clinical research grants are encouraged to include
minorities and women in study populations so research findings can be of benefit
to all people at risk of the disease or condition under study. It is
recommended that applicants place special emphasis on including minorities and
women in studies of diseases, disorders, and conditions that disproportionately
affect them. This policy applies to research subjects of all ages. If women or
minorities are excluded or poorly represented in clinical research, the
applicant should provide a clear and compelling rationale that shows inclusion
is inappropriate.

1.F. Inclusion of Children as Participants
in Clinical Research

FDA regulations at 21 CFR part 50, subpart D contain additional requirements
that must be met by IRBs reviewing clinical investigations regulated by FDA and
involving children as subjects. FDA is part of HHS; accordingly, the research
project grants under this program are supported by HHS, and HHS regulations at
45 CFR part 46, subpart D also apply to research involving children as
subjects.

HHS issued final modification to the Standards for Privacy of Individually
Identifiable Health Information, the Privacy Rule, on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the HHS
Office for Civil Rights (OCR).

Decisions about applicability and implementation of the
Privacy Rule reside with the researcher and his/her institution. The OCR Web
site http://www.hhs.gov/ocr/
provides information on the Privacy Rule.

1.H. Healthy People 2020

PHS is committed to achieving the health promotion and disease prevention
objectives of Healthy People 2020, a PHS-led national activity for setting
priority areas. This Funding Opportunity Announcement is related to one or more
of the priority areas. Potential applicants may obtain a copy of Healthy People 2020.

1.I. Smoke-Free Workplace

The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition, Public
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care, or early childhood
development services are provided to children. This is consistent with the PHS
mission to protect and advance the physical and mental health of the American
people.

1.J. Authority and Regulation

This program is not subject to the intergovernmental review requirements of
Executive Order 12372. FDA's research program is
described in the Catalog of Federal Domestic Assistance (CFDA), No. 93.103 http://www.cfda.gov/.

FDA will support the clinical studies covered by this
notice under the authority of section 301 of the PHS Act as amended (42 U.S.C.
241) and
under applicable regulations at 42 CFR Part 52 and 45 CFR Parts 74 and 92. All
grant awards are subject to applicable requirements for clinical investigations
imposed by sections 505, 512, and 515 of the act (21 U.S.C. 355, or 360e) or
safety, purity, and potency for licensing under section 351 of the Public
Health Service Act (the PHS Act) (42 U.S.C. 262), section 351 of the PHS Act,
including regulations issued under any of these sections.

All human subject research regulated by FDA is also subject
to FDA's regulations regarding the protection of human subjects (21 CFR Parts
50 and 56). Applicants are encouraged to review the regulations, guidance, and
information sheets on human subject protection and Good Clinical Practice
available on the Internet at http://www.fda.gov/oc/gcp/.

The applicant is referred to HHS regulations at 45 CFR
46.116 and 21 CFR 50.25 for details regarding the required elements of informed
consent.

All awards will be subject to all policies and
requirements that govern the research grant programs of the PHS as incorporated
in the HHS
Grants Policy Statement, dated January 1, 2007.